Project Summary/Abstract The objectives of this proposal are to continue to enhance our understanding of the effects of fluoride (F) and other factors on dental caries and bone development (mass, structure, micro-structure, and strength) by extending our assessments of the unique Iowa Fluoride Study(IFS)/Iowa Bone Development Study(IBDS) cohort into the transition period of young adulthood (age 27). The IFS, in its 27th year, has investigated the effects of F, diet, and other factors on dental caries and fluorosis at ages 5, 9, 13, 17, and 23 (in progress), contributing to our understanding of F intakes and timing of risk for dental fluorosis, associations of intakes of sugar-sweetened beverages with caries incidence, and caries-preventive effects of F exposures to age 17. The IBDS, in its 21st year, has investigated the effects of physical attributes, physical activity, F, diet, and other factors on bone measures at ages 5, 8, 11, 13, 15, 17, 19 and 23 (in progress). We have reported on the strong associations of childhood physical activity with improved bone outcomes in adolescence and the lack of evidence of harm from fluoride intakes, despite claims of fluoridation opponents. In the proposed extension, we will obtain age 27 bone outcomes using Dual-energy X-Ray Absorptiometry (DXA), Peripheral Quantitative Computed Tomography (pQCT), and Multi-Detector Computed Tomography (MDCT) and determine dental caries prevalence and incidence. We will collect detailed fluoride, diet, alcohol, tobacco, physical activity, sedentary behaviors, sleep, and body composition data, and relate the many explanatory variables to study outcomes, both at age 27 and the change from age 23 to 27. We will: 1)Characterize changes in cortical (Ct) and trabecular (Tb) bone micro-structure and strength from age 23 to 27 using MDCT of the distal tibia, 2) Determine the impact of changes in physical attributes (e.g., weight, adi- pose tissue, muscle, health status) and lifestyle behaviors (e.g., physical activity, sedentary behaviors, F and diet) on changes in micro-structure and strength from ages 23 to 27, 3) Assess the relationships of longitudinal patterns of F and dietary intakes (from birth to age 27) and physical attributes and lifestyle behaviors (from ages 5 to 27) with bone mass, structure, micro-structure, and strength at age 27 using DXA, pQCT, and MDCT, and 4) Assess the relationships of F, diet, and other factors with caries incidence from ages 23 to 27. Early adulthood involves major lifestyle behavior changes and is the time period when bone status establishes future risk for osteoporosis and bone fractures. However, critical gaps remain in understanding the effects of fluoride and other modifiable and non-modifiable factors on early adult caries and bone measures. Continued follow-up of the IFS/IBDS cohort in early adulthood with emphasis on bone micro-structure and strength, and dental caries incidence, will provide major insights into the relative importance and timing of explanatory factors on bone development and strength, and caries, establishing a strong foundation for improving the design of future strategies and interventions to optimize skeletal and oral health.